Here are some frequently asked questions about Addison’s disease and the Understanding the Genetics of Addison’s Disease in PWDs research study starting May 2021.
1. What is the difference between primary Addison’s disease and secondary Addison’s disease?
Primary Addison’s disease occurs when the adrenal gland cannot produce certain hormones normally because the outer layer of the adrenal gland is destroyed, most often by an autoimmune reaction. Secondary Addison’s disease occurs when problems with other organs (typically the pituitary gland) fail to stimulate the adrenal gland normally, but the adrenal gland itself is fine. Secondary Addison’s disease is extremely rare in dogs.
2. My dog participated in the Addison’s disease autoantibody study conducted by Dr. Friedenberg, beginning in 2018. Is my dog needed for this genetics study as well?
If your dog participated in the prior Addison’s autoantibody study funded by The Foundation, your dog’s DNA data is archived in Dr. Friedenberg’s lab. Contact his lab at firstname.lastname@example.org and they can advise whether any additional information is needed for your dog to participate in this genetics study.
3. How does your study plan to capture data regarding PWDs who may have multiple endocrine organs affected?
We are asking all dogs who participate in this study to take a short survey that includes a question regarding other co-morbidities, including other endocrine disorders. So, if we do happen to see that a lot of owners are reporting multiple autoimmune diseases in their Addisonian dogs, we will at least have that information in our study and can follow up for more detail at some point.
4. Does your research plan to investigate genes like those in APS-2 (autoimmune polyendocrine syndrome, type II)?
APS-2 is a human disease which has not been recognized in dogs. In APS-2 the main genetic link is with the HLA genes (human leukocyte antigens). As part of this study, we will be evaluating the analogous genes in dogs (DLA genes or dog leukocyte antigens) – in fact, this is Aim #2 of the study.
5. What prior research has been done on Addison’s disease in PWDs that could help support this study?
There have only been two papers published on Addison’s disease in PWDs, both of which were published 15 years ago. One study examined pedigrees of PWDs with and without Addison’s disease and concluded that the disease is likely genetic in the breed. This study also suggested that genes may explain only half of the risk of developing Addison’s disease, meaning that other factors besides genes may be at play.
A second study used a set of genetic markers called microsatellites to try to identify which parts of the genome might be associated with Addison’s disease in PWDs. This study found two broad regions of the genome that were linked with the disease but did not pinpoint any causative genes or gene mutations.
6. How will this study be different from prior research?
This study will take advantages of newly developed marker arrays that are 200-fold denser than the ones available in 2006. This should allow Dr. Friedenberg and his team to get closer to regions of interest across the genome. This study will also take advantage of whole genome sequencing, a technology that was not available in 2006. Additionally, this study will include an analysis of the role of the dog leukocyte antigen (DLA) in the development of Addison’s disease in PWDs, and will also benefit from prior data Dr. Friedenberg has collected from Standard Poodles. Standard Poodles are the most highly related breed to PWDs, and this breed also has a very high incidence of Addison’s disease.
7. Are you able to benefit from any published work from the Georgie Project?
Unfortunately, there is no data remaining from the Georgie Project, a study conducted by Dr. K. Gordon Lark at the University of Utah, and nothing has been published from the Georgie Project since 2006. However, we will certainly consider those findings as we carry out this study.
8. Is it possible to get access to the archive of data collected over the years associated with the Georgie Project?
Dr. Friedenberg reached out to the researchers involved in the Georgie Project to inquire if there might be an opportunity to share DNA and archived data. Sadly, the lab tech associated with Georgie reports that all the DNA samples were lost to a freezer malfunction and all other tissue has since disappeared. To date no one has been able to track down and SNP genotype data. The lab tech did share the spreadsheet of more than 300 PWDs in the project and (based on the spreadsheet) very few dogs had Addison’s disease.